Polypropionate-derived natural products can function as antibiotics, ionophores and pheromones. The development of highly diastereoselective and enantioselective methods for the synthesis of these substances permits new techniques for analog synthesis and the advancement of the study of organic reaction mechanisms. Using Claisen rearrangements and palladium- mediated alkylations developed during the present granting period, efforts currently underway will be continued to test the efficacy of this new methodology in the synthesis of several physiologically-active substances. Two antibiotics, elaiophylin, in particular its physiologically- active aglycones, and protomycinolide IV, will be the subjects of synthetic studies that will test our method for polypropionate synthesis and carbon-carbon bond macrocyclization. In the area of ionophores, synthetic studies on calcimycin and X-14885-A, important ion transport agents in biological systems, will be conducted. The denticulatins are marine polypropionate natural products that are structurally related to putative biogenetic precursors of the antimicrobial diemenesins. Synthetic efforts directed toward their synthesis will aid in the study of the mechanism of their formation. The anti-cholesteremic agent, heptelidic acid, provides an opportunity to study the mechanism of intramolecular palladium- mediated alkylations of vinyl epoxides and to prove the absolute configuration of this substance by synthesis. All of these projects are currently under investigation.